1. Field of the Invention
The present invention relates to a system and method for growing molluscum contagiosum virus (MCV) in human keratinocytes and, more specifically, for growing MCV in human keratinocytes through a xenograft to an immunocompromised host.
2. Description of Related Art
Molluscum contagiosum virus (MCV) causes an asymptomatic, indolent, harmless infection of human skin. However, in people with impaired immunity, especially in people with acquired immune deficiency syndrome (AIDS), MCV often becomes morbid with the development of many nodules some of which are large in size.
MCV is a member of the parapoxvirus family, along with orf virus, pseudocowpox (milker's nodule) virus, yaba virus and tanapox virus. MCV can be identified in skin biopsy samples by the presence of large intracytoplasmic inclusion bodies within infected keratinocytes. MCV lacks known close viral relatives and is serologically distinct from any other characterized pox virus. Fields BN and Knipe DM (eds.) Fields Virology 2nd Ed. Raven Press, New York. 1990, p. 31. Purified virions of MCV resemble those of vaccinia, a member of the orthopox virus group, in morphology, physical properties and chemical composition. Fields BN and Knipe DM (eds.) Fields Virology 2nd Ed. Raven Press, New York. 1990, p. 2130. However, although the vaccinia virus has been readily grown in culture, successful growth of MCV in culture has been elusive.
The difficulty associated with growing MCV in culture appears to be due to a defect in the expression of the genome in MCV. Mouse embryo cells infected with vaccinia have been shown to synthesize viral RNA and polypeptides. The same cells infected with MCV do not synthesize viral RNA and viral polypeptides. Shand, et al., J. Gen. Virol. (1976) 33:281-295. In culture, MCV has been shown to induce a nontransmissible cytopathic effect, but does not produce infectious progeny. Francis, et al., J. Virology (1976) 19:382-388. With the exception of one report (Buller, et al., Virology (1995) 213:655-659), attempts to grow MCV off a human host have repeatedly failed. For example, MCV was found not to grow on the chorioallantoic membrane of chick embryos, on normal human skin grafted onto the chorioallantoic membrane or in cultures of human fetal skin. Postlethwaite, Arch Environ Health (1970) 21:432-452. MCV has been found not to grow following inoculation into the skin, footpad, peritoneal cavity or brain of hairless mice. MCV has also been found not to grow in cultures of human embryonic liver or lung or in cultures of African green and cynomolgus monkey kidney cells or in cultures of human amnion and human foreskin. Postlethwaite, Arch Environ Health (1970) 21:432-452.
Failed attempts to grow MCV in the skin or other tissues of mice, guinea pigs, rabbits, sheep, apes and chimpanzees have also been reported. Warren J: Infections of minor importance: Molluscum contagiosum. In Rivers T M, Horsfall Jr F L: Viral and Rickettsial Infections of Man, 3rd Ed. Pitman Medical Publishing Co Ltd, London, 1959, pp. 908-909. Failed efforts to grow MCV in tissue culture from explants of diseased skin from patients with molluscum contagiosum and in organ cultures of healthy adult human skin inoculated with extracts of MCV papules have also been reported. Prose, et al., Am. J. Path. (1969) 55:349-366.
In view of the difficulties associated with growing MCV in host cells, a need currently exists for a method and host system for growing MCV. A further need exists for a system and method for growing MCV in human cells.